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Alteration in the Yap Signaling Pathway in Cataractous Human Lens Epithelium
Prakash Thushmitha1,2, Pandi Saranya1, Madhu Shekhar3
1Department of Immunology and Stem Cell Biology, Aravind Medical Research Foundation, Madurai, Tamil Nadu, India.
Purpose:
The loss of SOX2+GJA1- lens epithelial stem cells, along with a decrease in sphere-forming ability, was observed in the central zone of cataractous lenses. Nuclear localization of Yes-associated protein (YAP) has been associated with stemness in various tissues, and its conditional knockout was reported to develop cataract in mice. This study aims to investigate the expression of YAP and SOX2, along with other YAP signaling genes, in the anterior human lens epithelium of normal and cataractous lenses.
Methods:
Whole mounts of human anterior lens epithelium from normal and cataract lenses were immunostained for SOX2, YAP, and α-SMA, followed by confocal microscopic analysis. Further, the expression of YAP signaling genes was analyzed by Western blot.
Results:
Nuclear expression of SOX2 and YAP was identified in the central (7.25 ± 3.63% of cells) and equatorial (9.15 ± 6.09% of cells) zones of normal lens epithelium. Such cells were absent in cataractous lenses along with a significant reduction in nuclear YAP expression. Western blot analysis confirmed the increased pYAP/YAP ratio and decreased MST2 and LATS1 in cataractous lens compared to normal lens epithelium. Furthermore, α-SMA expression was elevated in cataractous lens epithelium, indicating its association with cataract development.
Conclusion:
The absence of SOX2+YAP+ cells in cataractous lenses indicated the possible association between stem cells and cataract development. Further studies are essential to elucidate the role of YAP signaling in the pathogenesis of cataract.
Insights
Loss of SOX2+YAP+ lens stem cells correlates with cataract development. Reduced nuclear YAP and altered YAP signaling pathways were observed in cataractous human lenses, suggesting a role in disease pathogenesis.
Area of Science:
- Ophthalmology
- Stem Cell Biology
- Molecular Biology
Background:
- Lens epithelial stem cells (SOX2+) are crucial for maintaining lens transparency.
- Nuclear Yes-associated protein (YAP) is linked to stemness and its disruption can cause cataracts.
- Cataract involves the loss of specific stem cell populations in the lens epithelium.
Purpose of the Study:
- To investigate the expression of YAP, SOX2, and YAP signaling pathway genes in human anterior lens epithelium from normal and cataractous lenses.
- To determine the correlation between SOX2+YAP+ cells and cataract development.
- To explore the role of YAP signaling in the pathogenesis of human cataracts.
Main Methods:
- Immunohistochemistry and confocal microscopy were used to analyze SOX2, YAP, and α-SMA expression in whole-mount human lens epithelium.
- Western blot analysis was performed to assess the expression of YAP signaling pathway components (pYAP/YAP ratio, MST2, LATS1).
Main Results:
- SOX2+YAP+ cells were present in normal lens epithelium but absent in cataractous lenses.
- Nuclear YAP expression was significantly reduced in cataractous lenses.
- Elevated pYAP/YAP ratio and α-SMA, with decreased MST2 and LATS1, were observed in cataractous lenses.
Conclusions:
- The absence of SOX2+YAP+ cells in cataractous lenses suggests their involvement in cataract development.
- YAP signaling pathway alterations are associated with human cataract pathogenesis.
- Further research is needed to fully understand YAP's role in cataract formation.
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